The ugly side of amphetamines: short- and long-term toxicity of 3,4-methylenedioxymethamphetamine (MDMA, ‘Ecstasy’), methamphetamine and d-amphetamine

Amphetamines like speed, ice, and ecstasy are widely abused for their euphoric and stimulant effects. While animal studies show strong evidence that MDMA causes chronic neurotoxicity, the physiological consequences in humans remain unclear. Differences in metabolism and pharmacokinetics between species and animal strains make it difficult to design realistic human dose paradigms in animal research. This review examines amphetamine toxicity, especially MDMA toxicity, in the context of human disease, setting aside confounding factors such as polydrug use and drug purity.

Study at a glance

Abstract

Abstract Amphetamine (‘Speed’), methamphetamine (‘Ice’) and its congener 3,4-methylenedioxymethamphetamine (MDMA; ‘Ecstasy’) are illicit drugs abused worldwide for their euphoric and stimulant effects. Despite compelling evidence for chronic MDMA neurotoxicity in animal models, the physiological consequences of such toxicity in humans remain unclear. In addition, distinct differences in the metabolism and pharmacokinetics of MDMA between species and different strains of animals prevent the rationalisation of realistic human dose paradigms in animal studies. Here, we attempt to review amphetamine toxicity and in particular MDMA toxicity in the pathogenesis of exemplary human pathologies, independently of confounding environmental factors such as poly-drug use and drug purity.